The Role of Adenosine A1 and A2A Receptors in the Caffeine Effect on MDMA-Induced DA and 5-HT Release in the Mouse Striatum
Anna Górska, Krystyna Gołembiowska
Neurotoxicity Research November 13, 2014 DOI: 10.1007/s12640-014-9501-0 via OpenAlex
Summary
AI-generated from the abstractCaffeine worsens the increase in dopamine and serotonin release caused by MDMA (ecstasy) in the mouse striatum. Blocking adenosine A1 or A2A receptors with selective antagonists mimics caffeine's effect, with the A2A antagonist being more potent. This suggests that caffeine exacerbates MDMA's neurochemical effects and potential toxicity through adenosine receptor blockade, not through monoamine oxidase inhibition.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Caffeine MDMA DPCPX KW 6002 CGS 15943A |
| Dose | 10 mg/kg caffeine, 20 or 40 mg/kg MDMA |
| Topics | MDMA Serotonin |
| Keywords | Caffeine Neurochemistry Striatum Adenosine receptor |
| Citations | 36 |
| Key finding | Caffeine exacerbates MDMA-induced dopamine and serotonin release in the mouse striatum, an effect mediated by blockade of adenosine A1 and A2A receptors. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") popular as a designer drug is often used with caffeine to gain a stronger stimulant effect. MDMA induces 5-HT and DA release by interaction with monoamine transporters. Co-administration of caffeine and MDMA may aggravate MDMA-induced toxic effects on DA and 5-HT terminals. In the present study, we determined whether caffeine influences DA and 5-HT release induced by MDMA. We also tried to find out if adenosine A1 and A2A receptors play a role in the effect of caffeine by investigating the effect of the selective adenosine A1 and A2A receptor antagonists, DPCPX and KW 6002 on DA and 5-HT release induced by MDMA. Mice were treated with caffeine (10 mg/kg) and MDMA (20 or 40 mg/kg) alone or in combination. DA and 5-HT release in the mouse striatum was measured using in vivo microdialysis. Caffeine exacerbated the effect of MDMA on DA and 5-HT release. DPCPX or KW 6002 co-administered with MDMA had similar influence as caffeine, but KW 6002 was more potent than caffeine or DPCPX. To exclude the contribution of MAO inhibition by caffeine in the caffeine effect on MDMA-induced increase in DA and 5-HT, we also tested the effect of the nonxanthine adenosine receptor antagonist CGS 15943A lacking properties of MAO activity modification. Our findings indicate that adenosine A1 and A2A receptor blockade may account for the caffeine-induced exacerbation of the MDMA effect on DA and 5-HT release and may aggravate MDMA toxicity.